New Alzheimer's risk genes

The research was led by Alzheimer’s Society research fellow Dr Rebecca Sims from Cardiff University and published in the leading scientific journal Nature Genetics.

Dr Sims and her colleagues compared the DNA of tens of thousands of people with Alzheimer’s to people of the same age who do not have the disease. This was to understand whether there were any genetic differences between the two groups that could pinpoint why some people are more at risk of developing the disease. They discovered two genes with rare changes that were associated with risk of Alzheimer’s. A change in a gene called PLGC2 was found to be protective. Changes in another gene, ABI3, were found to increase the risk of developing Alzheimer’s.

Both of these genes are part of the brain’s immune system and are found in specialised immune cells called microglia. There is emerging evidence that the immune system plays a key role in the development of Alzheimer’s and researchers are particularly interested in the microglia, as one of their functions is to ‘mop up’ damaging deposits in the brain. This study also complements several others that have found genes related to the microglia that might affect a person’s Alzheimer’s risk – these immune cells could be making a direct contribution to the disease’s development.

Working out how different genes and proteins interact in the brain when someone has Alzheimer’s is important. This information helps researchers to understand more about the underlying causes of the disease and can point us towards potential areas to target when developing treatments.

Dr Sims said, ‘In addition to identifying two genes that affect the risk of developing Alzheimer’s disease, our new research reveals a number of other genes and proteins that form a network likely to be important in its development.’

Dr Doug Brown, Director of Research and Development at Alzheimer’s Society, said, ‘Over 60% of people with dementia have Alzheimer’s disease, yet despite its prevalence we still don’t fully understand the complex causes.

‘The discovery of two new risk genes for Alzheimer’s is an exciting advance that could help to deepen our understanding of what happens in the brains of people with the disease.

‘Insights like this are vital to help unravel the complexities of Alzheimer’s disease and show researchers where to focus their efforts in the search for new, effective treatments.’

Cardiff University is the site of one of the six centres of the UK Dementia Research Institute. This centre will use discoveries in genetics and the immune system, such as the ones made by Dr Sims, as a starting point for understanding the disease and producing new therapies.